组织弹性调节心脏起器细胞自动性的弹性
Young Hwan Choi1,2, Jing Leng1,2, Jinqi Fan1,2
1The Blalock-Taussig-Thomas Pediatric and Congenital Heart Center, Johns Hopkins Children's Center, Baltimore, Maryland, United States.
概括
更硬的凝水凝增强了心脏起器细胞的自动性和Hcn4表达. 这项研究为研究心律和纤维化提供了一个新的体外模型.
科学领域:
- 心血管生物学 心血管生物学
- 生物材料科学 生物材料科学
- 细胞机械生物学 细胞机械生物学
背景情况:
- 组织弹性对心脏功能至关重要,但在刚性塑料上的传统细胞培养限制了对其影响的研究.
- 心脏传导系统,特别是起器细胞,需要特定的机械环境.
- 凝水凝提供了一个可调节的平台,以模仿细胞培养的组织弹性.
研究的目的:
- 为了研究不同组织度对心脏起器细胞功能的影响.
- 为了利用转录因子重编程的心脏起器细胞在具有定义弹性的凝水凝上.
- 在心肌细胞和导电系统细胞中建模机电反.
主要方法:
- 在控制弹性的凝水凝上培养心脏起器细胞 (例如14kPa).
- 通过节律收缩和细胞内 (Ca2+) 过渡物来测量细胞自动性.
- 评估关键离子通道 (Hcn4) 和间隙结 (Cx43) 的基因表达.
- 分析Ca2+的短暂传播和纤维细胞增殖.
主要成果:
- 增加的矩阵刚度 (14kPa) 增强了心脏起器细胞的自动性,由节奏收缩和Ca2+振荡证明.
- 更硬的矩阵导致Hcn4表达增加,Cx43表达减少.
- 在更硬的水凝上,Ca2+的短暂传播速度较慢,模仿原生组织,并与纤维细胞增殖有关.
- 在刚性板上培养导致不规则的收缩和长时间的Ca2+短暂持续时间.
结论:
- 心脏起器细胞自动性是通过在心肌弹性的生理范围内的更硬的细胞外基质基质来增强的.
- 这种可调节的水凝方法为研究心脏机电反提供了一个生理上相关的体外模型.
- 这些发现为研究心律调节和纤维化在心脏病中的作用提供了一个框架.
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